The impact of prenatal mental health on birth outcomes before and during the COVID-19 pandemic in Anhui, China

Adverse birth outcomes remain challenging public health problems in China. Increasing evidence indicated that prenatal depression and anxiety are associated with adverse birth outcomes, highlighting the importance and severity of prenatal depression and anxiety in China. The COVID-19 pandemic is likely to further exacerbate prenatal mental health problems and increase the risk of adverse birth outcomes. The aim of this study is to assess and compare the impacts of prenatal mental health issues on birth outcomes before and during the COVID-19 pandemic in Ma’anshan, Anhui, China. Participants in this study were women who visited local maternal and child health hospitals in Ma’anshan, Anhui, China. Two independent sets of individual maternal data (npre-pamdemic = 1148; npandemic = 2249) were collected. Prenatal depression and anxiety were measured online using the Edinburgh Postnatal Depression Scale (EPDS) and the General Anxiety Disorder-7 (GAD-7). Adverse birth outcomes were determined using hospital-recorded infant birth weight and gestational age at delivery. In this study, we found that the pandemic cohort had lower mean EPDS and GAD-7 scores than the pre-pandemic cohort. The prevalence of prenatal depression (14.5%) and anxiety (26.7%) among the pandemic cohort were lower than the pre-pandemic cohort (18.6% and 36.3%). No significant difference was found in the prevalence of adverse birth outcomes comparing the two cohorts. Prenatal depression was associated with small gestational age only in the pandemic cohort (OR = 1.09, 95% CI 1.00–1.19, p = 0.042). Overall, this study highlighted an association between prenatal depression and small for gestational age in Anhui, China. Addressing prenatal depression may thus be key in improving birth outcomes. Future studies could focus on potential causal relationships.


Introduction
Pregnancy is a critical time that precedes motherhood for many women.Women face a multitude of different biological and psychological changes and contend with changes in familial and societal social status [1].These changes can be overwhelming and lead to some types of mental health symptoms and disorders [1].China has a high rate of prenatal depression and anxiety compared to other countries [2].Studies have shown the prevalence of prenatal depression in China to be between 3.6% to 40.2%, and prenatal anxiety to be between 1.8% to 42.1%, compared to the global average of 18.2% to 24.6% for prenatal depression and 7.4% to 12.8% for prenatal anxiety [1,3].
Disasters and infectious disease outbreaks have been known to increase the risk of developing depression and anxiety [4,5].Thus, with the significant threats from the coronavirus disease 2019 (COVID-19) pandemic, pregnant women could be at an even higher risk of developing prenatal depression and anxiety [4,5].In China, some studies suggested that the rates of prenatal mental health issues have increased since the declaration of the pandemic.For example, Dong et al. suggested that the level of depression among pregnant women has significantly increased during the COVID-19 pandemic (50.6%) compared to the period before the pandemic (3.5% to 8.2%), with nearly 27% of the pregnant women experiencing moderate to severe depression [6].Another study reported the estimated prevalence of prenatal anxiety increased from 15.2% pre-pandemic to 37.0% during the pandemic [7].Anhui has the highest prevalence of perinatal depression (33%) in mainland China, according to a meta-analysis that examined 95 studies across 23 Chinese regions [3,8].
Prenatal depression and anxiety have been found to be associated with adverse birth outcomes, including preterm birth, low birth weight and small for gestational age [1,9].Adverse birth outcomes are the leading causes of neonatal deaths and under-five years mortality and serve as key risk factors for the development of neurological damage, respiratory diseases, visual and hearing impairment, later-life morbidities [10][11][12].Using the psychobiobehavioral model, researchers have hypothesized that complex psychological, biological, and behavioral factors explain the association between adverse birth outcomes and their associated morbidities [13].A stressful event, such as the pandemic, could trigger an increased risk of developing adverse birth outcomes via stress pathways [14,15].
To our knowledge, there has been no original research exploring the impacts of prenatal depression and anxiety on birth outcomes before and during the pandemic in China [16].This epidemiological study aims to explore the association between prenatal mental health issues and birth outcomes and highlight key findings concerning the psychosocial impacts of pregnancy and related risk factors before and during the COVID-19 pandemic, to help mitigate adverse birth outcomes in other public health emergencies.

Study setting, population, and data collection
This study was conducted in the city of Ma'anshan, Anhui province, China.Anhui is a landlocked province in the East China region, bordered by Hubei province which is the epicenter of the COVID-19 pandemic in China [17,18].As of March 22, 2023, Anhui has reported more than 70,000 cases [19].
Participants were women aged of 18 years and above who visited local maternal and child health hospitals in Ma'anshan.Maternal data were collected at two timepoints, from different cohorts: 1) Pre-pandemic data (n = 1148) were collected between May 27 and September 11, 2019; and 2) Pandemic data (n = 2249) were collected between April 27 and August 20, 2020.The data collection process was carried out by a team trained in the use of the tools, and followed data collection procedures and protocols [8].Sociodemographic, prenatal depression, and anxiety measures were administered using online self-report questionnaires.Birth outcome measures were collected from existing medical records.Medical records were retrieved analyses of sociodemographic risk factors for prenatal depression and anxiety, and analyses of the relationship between prenatal depression and anxiety and birth outcomes (i.e., multivariable linear regression and logistic regression).T-tests and chi-square tests were conducted to compare characteristics between groups.The stepwise method was used to build the model.All statistical analyses were performed using STATA/BE 17.0.A p-value <0.05 was considered statistically significant.

Ethics statement
This study was approved by the Research Ethics Boards of the University of Alberta (Pro00099276; Pro00087163), University of Calgary (Pro00099276_AME6; REB19-0336), York University (2020-117; 2018-179) and Anhui Medical University (2020H001).All participants were offered mental health resources and further counseling provided by the Mom's Good Mood project [8].

Characteristics of study population
A total of 3438 participants were recruited across the two study timepoints/cohorts.Of the 1189 participants recruited in the pre-pandemic cohort, 1148 (96.6%) participants responded to the survey.2249 participants were recruited in the second cohort during the pandemic; all the 2249 provided a response to the survey.Although statistical tests showed significant differences between many variables, it is likely due to different samples size between the two.Otherwise, the two cohorts share similar distributions of demographic characteristics, with exception of household income and passive smoking (Table 1).
Prenatal depression and anxiety.The pandemic cohort was found to have significantly lower mean EPDS scores compared to the pre-pandemic cohort (5.4 vs 5.8) (Table 2).Furthermore, the prevalence of prenatal depression symptoms (i.e., EPDS score �9) in the pandemic cohort was 14.5%, which was 4.1% lower than the prevalence (18.6%) in the pre-pandemic cohort.As for prenatal anxiety, a similar trend appeared.The mean GAD-7 scores were significantly higher in the pre-pandemic cohort than it was in the pandemic cohort (3.8 vs 2.9).The prevalence of prenatal anxiety measured by the GAD-7 (i.e., GAD-7 score�5) was also higher in the pre-pandemic cohort (36.3%) than it was in the pandemic cohort (26.7%).Additionally, the rates of different severity levels of depression and anxiety symptoms were also lower in the pandemic cohort compared to the pre-pandemic cohort.
Risk factors of prenatal depression and anxiety.Pre-pandemic, we found that higher socioeconomic status was significantly associated with lower mean EPDS scores (β = -0.30,95% CI: -0.44 to -0.17, p<0.001).This indicates that participants with higher incomes experienced less severe depression symptoms, compared to people with lower socioeconomic status in the multivariable model.Participants who reported having more people in the household, not being married, formerly smoked, or were still smoking, or had an unexpected pregnancy at the time were found to be at greater risk of experiencing higher levels of depressive symptoms (Table 3).As for prenatal anxiety, we found that older pregnant women had lower GAD-7 scores (β = -0.05,95% CI: -0.1, -0.004, p = 0.031) in the pre-pandemic cohort.Participants who were not married, consuming alcohol, exposed to passive smoking, had an unexpected pregnancy, and reported a prior history of adverse pregnancy outcomes were likely to have higher GAD-7 scores (Table 3).
In the pandemic cohort, we found that women in their second or third trimesters, with higher socioeconomic statuses and who were of older ages, had lower mean EPDS scores in the multivariable model (Table 4).On the other hand, exposure to passive smoking, having a history of alcohol consumption, a history of mental health issues, higher education levels, reporting an unexpected pregnancy, and more people in the household were found to be risk factors associated with higher EPDS scores.Results showed that women who reported drinking had higher overall mean EPDS scores compared to women who did not drink.Furthermore, we found a significant interaction between trimester and alcohol consumption.Mean EPDS scores, among women who reported drinking, were highest in the first trimester compared to in the second and third trimesters.As for prenatal anxiety, results showed that women who were in their second or third trimester, who reported higher socioeconomic status and were older, had lower mean GAD-7 scores.Exposure to passive smoking, drinking alcohol, prior adverse pregnancy outcomes, history of mental health issues, and greater household size were risk factors for higher mean GAD-7 scores.Adverse birth outcomes.There was no significant difference in the mean birth weight between pre-pandemic and pandemic cohorts.Although the rate of low birth weight was slightly lower in the pandemic cohort, and the rate of small for gestational age was slightly higher in the pandemic cohort, the differences was not significant (Table 5).
Association between prenatal mental health issues and adverse birth outcomes.In the pre-pandemic cohort, birth weight, gestational age, and small for gestational age were not significantly associated with prenatal depression or anxiety (Tables 6 and 7).However, participants' prepregnancy BMI, marital status, household income, and types of conception were significantly Overall, results collected during the pandemic showed that prenatal depression was associated with a higher risk of having small for gestational age infants, with the key interactions between trimester and EPDS, in the model (Table 8).Women who were in their first trimester, with higher EPDS scores, were at the highest risk of giving birth to infants with small for gestational age weight, compared to women in the second and third trimesters.Women who are in their third trimester, with higher EPDS scores, had the lowest risk of small for gestational age, compared to women in the other two trimesters.Prenatal depression was not significantly associated with low birth weight or preterm birth.Prenatal anxiety was also not associated with any adverse birth outcomes, in this study (Table 9).
Multiparous was significantly associated with infants' birth weight, gestational age and small for gestational age.Participants' who had higher pre-pregnancy BMI was associated with higher infants' birth weight.Participants with older age was associated with lower infants' gestational age (Tables 8 and 9).

Summary of findings
This study assessed the prevalence of prenatal depression, anxiety, low birth weight, preterm birth, and small for gestational age weight.We also identified potential sociodemographic risk factors for these mental health and birth outcomes before and during the COVID-19 pandemic in Ma'anshan, Anhui, China, as well as explored the relationship between prenatal mental health and birth outcomes.We found that the prevalence of prenatal depression and anxiety was lower during the pandemic compared to in the pre-pandemic period.The prevalence of each adverse birth outcome was not significantly different between the two cohorts, although the prevalence of low birth weight and small for gestational age was slightly lower during the pandemic.Furthermore, we only found prenatal depression was significantly associated with higher risk of small for gestational age during the pandemic period.Risk factors for prenatal depression and anxiety varied between pre-pandemic and pandemic periods.

Prenatal depression and anxiety
Compared to studies conducted before the COVID-19 pandemic using the same/similar screening tools, prenatal depression prevalence (18.6%) measured in this study was like that reported in another study also conducted in Anhui (19.1%) [21,30].Prenatal anxiety prevalence in our study (36.3%) before the pandemic was almost the same as reported in the cities of Shenyang, Zhengzhou, and Chongqing (36.4%) [31].During the pandemic, prenatal b Economic status compared to people around the participant, with 0 as the lowest and 10 the highest.
c No alcohol consumption is defined as not more than one drink of either 340ml of beer or 140ml of wine or 43ml of Chinese Baijiu.
d Adverse pregnancy outcomes include miscarriage, stillbirth, perinatal mortality, and birth defects. https://doi.org/10.1371/journal.pone.0308327.t003 depression prevalence was 14.5%, which was much lower than was reported in Wuhan (33.7%), the epicenter of the COVID-19 outbreak in China [23].The prevalence of prenatal anxiety during the pandemic, in our study, was 26.7%, which was different than in other parts of China, including Changzhou (31.7%),Guangzhou (19.0%), and Shenyang (11.8%) [32][33][34].Differences in depression and anxiety prevalence during the pandemic could be due to the localized severity of the pandemic across multiple cities [35], as well as the use of different screening tool cut-off points [36].b Economic status compared to people around the participant, with 0 as the lowest and 10 the highest.c No alcohol consumption is defined as not more than one drink of either 340ml of beer or 140ml of wine or 43ml of Chinese Baijiu.
d Adverse pregnancy outcomes include miscarriage, stillbirth, perinatal mortality, and birth defects. https://doi.org/10.1371/journal.pone.0308327.t004 An interesting finding was that the prevalence of prenatal depression and anxiety was lower in the pandemic cohort than it was in the pre-pandemic cohort.Many published studies reported higher rates of prenatal depression and anxiety during the pandemic compared to pre-pandemic periods.This is possibly due to the uncertainty regarding the effects of COVID-19 on fetal health, pandemic restrictions, and pandemic-related income loss [4,6,7,37].There were fewer studies that reported lower rates of prenatal mental health issues [38,39].Another longitudinal study conducted in China reported non-significant differences in anxiety and depression between pandemic and pre-pandemic periods [40].However, this study focused on the general population, rather than pregnant women.In our study, the reduction in prenatal depression and anxiety rates could be due to different factors.First, women may be more likely to receive more family support and care during their pregnancies, given household structures in China, which could have been protective [1,41].A study reported that increased social support increases people's resilience to stress, further leading to decreased risk of developing prenatal anxiety and depression [42].Second, social activities during the pandemic were limited in China.For instance, due to pandemic social restrictions, pregnant women no longer needed to go to work in-person, which may have translated into more time to focus on their pregnancy and family.Findings could also be due to the severity of the COVID-19 pandemic in Ma'anshan, which was lower compared to the cities examined in other studies that reported increased prenatal depression and anxiety [4,6,7,37].Another study reported that women from the pandemic's hardest-hit areas in China were more likely to experience anxiety [43].In addition, China actively, quickly, and strictly implemented COVID-19 management and control strategies to minimize the impact of the pandemic on the economy, society, production, and peoples' lives [44].These strategies may have eased stress and panic.It is also important to note that differences may have arisen in this study as the pre-pandemic and pandemic cohorts did not include the same participants.Differences, other than those assessed in the study, might also have impacted these results.Further longitudinal research is needed to explore changes in the prevalence of prenatal depression and anxiety across time in the same population.
In our study, we also assessed the risk factors of prenatal depression and anxiety.Like many other studies that reported significant associations between prenatal depression and alcohol consumption [13][14][15][16], we also found that women who reported drinking had overall higher mean EPDS scores than those who did not drink.This could be due to that women who did not drink are less likely to stress about the consequences of drinking on their fetus, but the ones who reported drinking might also experience more stress since they may worry about their drinking behavior could have damaged the development of the baby.However, several studies have reported no association between alcohol use and prenatal depression [45].The inconsistency in results could also be due to differences in measurement of depression and alcohol use.In addition, we only assessed general alcohol consumption status, rather than consumption during pregnancy.Thus, it is unclear if prenatal depression occurs after or prior to alcohol consumption.We also observed that mean EPDS scores were the highest among women in their first trimester compared to women in their second or third trimester.The first trimester is often a time of adjustment, which may lead to higher levels of stress.It could also be due to women in their first trimester often experiencing discomfort or severe pregnancy sickness, such as nausea.

Adverse birth outcomes and association with prenatal mental health issues
To our knowledge, this is the first study that explored and compared the impact of prenatal depression and anxiety on birth outcomes in China before and during the COVID-19 pandemic.Previous studies have largely been conducted before the pandemic or during the pandemic, but not in both time periods [16].Although some findings are inconsistent with prior results, this study contributes to the literature around potential pathways and impacts of prenatal depression and anxiety on birth outcomes, through the comparison of stress before and during a public health emergency.
In this study, we found that prenatal depression or anxiety was not significantly associated with lower birth weight, lower gestational age or small for gestational age in the pre-pandemic period after adjusting for other covariates.Similarly, many studies reported that prenatal depression or anxiety was not associated with an increased risk of low birth weight or decreases in birth weight, preterm birth, or small for gestational age [30,[46][47][48].However, in the pandemic cohort, small for gestational age was significantly associated with prenatal depression.This could be due to the imbalanced neuroendocrine caused by prenatal depression that has impacted on the fetal development.Experts hypothesize that depression during pregnancy may stimulate the hypothalamus-pituitary-adrenal (HPA) system and lead to hypo-or hypersecretion of cortisol and norepinephrine, decreasing uterine blood flow, leading to parturition, and impaired fetal development and growth [20,21,49].Similar findings on the association between small for gestational age and prenatal depression were also reported in other studies [30,[50][51][52][53][54][55][56][57][58].

Limitations
There are some limitations to this study.First, due to the nature of the data, this study only focused on exploring the association between prenatal mental health and birth outcomes, rather than a causal relationship between the two.Second, the pre-pandemic and pandemic cohorts differed in size.This is due to the fact that pre-pandemic data collection was part of another project.Separate sample size estimations were calculated for the pandemic cohort to explore prenatal depression and anxiety in relation to low birth weight, preterm birth, and small for gestational age weight.Women were recruited from the same region to ensure comparability, though this might affect the generalizability of these results.Third, prenatal depression and anxiety were assessed online using self-reported questionnaires.Although these tools have been demonstrated to have good reliability and validity in the Chinese population, the potential for reporting bias cannot be overlooked.The inclusion of clinical diagnoses might help to reduce this bias in future studies.

Conclusion
In this study, the prevalence of prenatal depression, anxiety and adverse birth outcomes was lower after the onset of the COVID-19 pandemic.A significant association between prenatal depression and small for gestational age during the pandemic was found.More research on prenatal depression and anxiety trends during the pandemic, as well as their impacts on birth outcomes, is needed.This type of research can help inform national plans, establish health priorities, and guide clinical and public health responses to COVID-19 and other future pandemics and disasters.

Table 1 .
(Continued) a Body mass index.bEconomicstatuscompared to people around the participant, with 0 as the lowest and 10 the highest.cNoalcoholconsumption is defined as not more than one drink of either 340ml of beer or 140ml of wine or 43ml of Chinese Baijiu.dInvitro fertilization.eIntracytoplasmicsperm injection.fAdverse pregnancy outcomes include miscarriage, stillbirth, perinatal mortality, and birth defects.https://doi.org/10.1371/journal.pone.0308327.t001associated with infants' birth weight in the multivariable model.For the gestational age outcome, participants' age, types of conception, and multi-parity were statistically significant in the adjusted model.Participants' pre-pregnancy BMI, number of people in the household, education, and multi-parity were significantly associated with small for gestational age.

Table 3 . Risk factors of prenatal depression and prenatal anxiety among the pre-pandemic cohort (n = 1148)-multivariable analysis.
a 95% confidence interval.

Table 4 . Risk factors of prenatal depression and prenatal anxiety among the pandemic cohort (n = 2249)-multivariable analysis.
a 95% confidence interval.

Table 6 . Association between prenatal depression and birth outcomes among the pre-pandemic cohort-multivariable models.
b Odds ratio.c Body mass index.d In vitro fertilization.e Intracytoplasmic sperm injection.

Table 7 . Association between prenatal anxiety and birth outcomes among the pre-pandemic cohort-multivariable models.
b Odds ratio.c Body mass index.d In vitro fertilization.e Intracytoplasmic sperm injection.

Table 8 . Association between prenatal depression and birth outcomes among the pandemic cohort-multivariable models.
a 95% confidence interval.bOdds ratio.cBody mass index.